While ABO/Rh(D) red blood cells (RBC)-matched transfusions are generally considered as safe, a significant risk of alloimmunization to non-A/B blood group antigens exists; especially in chronically transfused patients. Indeed, alloimmunization to non-A/B antigens can be so severe that RBC transfusion can no longer be safely administered without the risk of a potentially deadly immune haemolytic reaction. Currently, no satisfactory solutions exist either to prevent blood group alloimmunization or to cost-effectively treat patients with severe alloimmunization. To address this problem, we have pioneered the immunocamouflage of donor RBC. The immunocamouflaged (stealth) RBC is manufactured by the covalent grafting of biologically safe polymers to RBC membrane proteins. As a result of the grafted polymer, non-A/B blood group antigens are biophysically and immunologically masked. Of particular interest is the immunocamouflage of the Rh(D) antigen which could be used to improve blood inventory and transfusion safety. The polymer-modified RBCs are morphologically normal and, in mice, exhibit normal in vivo survival at immunoprotective grafting concentration. In this chapter, we explore both the biophysical and immunological consequences of the grafted polymers, explore the conditions in which they might be appropriately used, and describe the technology necessary to manufacture functional transfusable units of these cells within the clinical setting.
Part of the book: Transfusion Medicine and Scientific Developments